The objective of this research proposal is to define the importance of activation of the alternative pathway (A.P.) of complement in disease. We will determine the incidence of A.P. activation and the mechanisms of activation in certain autoimmune diseases, and idiopathic urticaria. We will attempt to isolate activators in the sera of some patients, characterize them and study mechanism of activation. Work initiated previously on the in vivo activation of A.P. by radiographic contrast media will be continued, particularly in mechanisms of in vitro activation. We intend to determine the incidence and significance of complement split products in serum and plasma in normal individuals and during disease activity. Finally, we will determine if certain tissue antigens or circulating antigen-antibody complexes of defined specificities activate the alternate pathway of complement. The methodology in these studies would involve the use of monospecific antibodies to complement proteins. Complement proteins will be quantitated by hemolytic assays as well as immunodiffusion and electrophoretic techniques. Activation of the alternative pathway will be assayed by using glutathione treated cells, specific complement depleted sera and by detecting breakdown products of factor B. In some experiments, immunofluorescent techniques will be used to demonstrate the presence of immunoglobulins and/or complement in different tissue preparations.